Transection of the direct cortico-motoneuronal pathway at the mid-cervical segment of the spinal cord in the macaque monkey results in a transient impairment of finger movements. Finger dexterity recovers within a few months. Combined brain imaging and reversible pharmacological inactivation of motor cortical regions suggest that the recovery involves the bilateral primary motor cortex during the early recovery stage and more extensive regions of the contralesional primary motor cortex and bilateral premotor cortex during the late recovery stage. These changes in the activation pattern of frontal motor-related areas represent an adaptive strategy for functional compensation after spinal cord injury.